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Triple-Negative Breast Cancer Spread and Prognosis: Brain, Liver, Lungs, and More

Medically reviewed by Maybell Nieves, M.D.
Written by Aminah Wali, Ph.D.
Posted on January 18, 2024

Cancer that starts in breast tissue unfortunately doesn’t always remain there. When breast cancer cells metastasize (spread beyond the original breast tumor) and form tumors in other parts of the body, it’s known as metastatic breast cancer or stage 4 breast cancer. (Cancer stages are sometimes noted with Roman numerals — in this case, stage IV.) Triple-negative breast cancer (TNBC) is more likely to metastasize and cause death compared to other breast cancer subtypes. Among people with metastatic TNBC, the spread of cancer through the body — and not the original tumor — is most often the cause of death.

TNBC is characterized by its unique molecular profile, aggressive nature, distinct metastatic patterns, and lack of targeted therapies. It’s called “triple-negative” because cancer cells lacks three hormone receptor proteins commonly seen in other types of breast cancer:

  • Estrogen receptor (ER)
  • Progesterone receptor (PR)
  • Human epidermal growth factor receptor 2 (HER2)

These proteins are used as targets in treating other types of breast cancer. Since they’re missing in TNBC, hormone therapies that target ER-, PR-, or HER2-positive breast cancers don’t work for TNBC. Fast growth and limited treatment options often lead to a poor prognosis (outlook). Once breast cancer cells spread to other parts of the body — known as distant metastasis — of people with TNBC, they’re about 12 percent as likely to be alive after five years compared to the general population.


One study showed that people whose TNBC first spread to the lungs lived longer than people whose cancer spread to other areas first.

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Your prognosis will depend, in part, on where in your body the distant tumors — called metastases — develop. In this article, we’ll go over other parts of the body TNBC commonly spreads to, symptoms to look out for, and how it may affect your prognosis. Your oncologist (cancer specialist) can help you understand more about metastatic TNBC and what your options are.

Read more about stage 4 TNBC survival rates and risk factors.

Liver Metastasis

It’s common for TNBC to spread to the liver. While this doesn’t always cause symptoms, liver metastasis can lead to a number of health problems, including:

  • Jaundice (which can cause yellowing of the eyes and skin)
  • Fever
  • Abdominal pain
  • Swelling in the legs
  • Lack of appetite or weight loss

To check for liver metastases, your doctor may order blood tests called liver function tests that measure how healthy your liver is. They might also use imaging techniques or take a biopsy (tissue sample) to see whether there are cancer cells in the liver.

A study conducted in Taiwan looked at overall survival rates in people with TNBC who had metastases in different organs. For each metastatic site, they measured median survival — this is the length of time after which half the people in that group were still alive. Researchers found that when cancer spread to the liver first, people had a median survival of 8.9 months (ranging from 3.5 to 14.4 months).

Bone Metastasis

In some cases of metastatic TNBC, the cancer can spread to the bones. This is more common in older people than in younger individuals with TNBC. Although bone metastasis doesn’t always cause problems, it might result in different symptoms, including:

  • Bones that break easily with normal activities
  • Bone pain
  • Neck and back pain
  • Problems when urinating or having a bowel movement
  • Feelings of weakness or numbness in the limbs

Cancer is more likely to spread to the bones in older people with triple-negative breast cancer than in younger people.

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Bone metastasis can also lead to hypercalcemia (high calcium levels in the blood). Hypercalcemia can cause problems like:

  • Nausea
  • Dehydration
  • Lack of appetite
  • Feelings of weakness or fatigue

If your doctor suspects your cancer has spread to the bones, they can use imaging tests like X-rays or bone scans to look for lesions (injuries) on your bones. They may also take a biopsy and examine the cells using a microscope to look for cancer in your bones.

Compared to other subtypes of breast cancer, TNBC is more likely to spread to other organs than to bones. However, there is still a risk. The study done in Taiwan found that, in about 23 percent of study subjects, the cancer spread to the bone first. This led to a median survival of 16.3 months (ranging from 11.7 to 20.8 months). Bone metastasis does occur in TNBC and may decrease a person’s chance of survival.

Lung and Pleural Metastases

The lungs are another common site of metastasis. Moreover, cancer may spread to the pleura, which is a sheet of tissue that wraps around the lungs. Lung and pleural metastases often occur together. When this happen, it may cause symptoms such as:

  • Frequent coughing
  • Coughing up of blood
  • Chest pain
  • Breathing difficulties
  • Chest infections

Lung and pleural metastases can also cause a pleural effusion — a buildup of fluid between the chest wall and the lungs. Pleural effusion can lead to a worse prognosis.

The Taiwanese study found that the prognosis for people with metastatic TNBC was better when the cancer first spread to the lungs instead of other parts of the body. The median survival time was 16.6 months (ranging from 10.3 to 22.9 months) among this group.

When the cancer spread to the pleura first, median survival was 7.5 months (ranging from 2.8 to 12.3 months).

Brain Metastasis

The risk of brain metastasis is a major concern for people with breast cancer. Compared to other types of breast cancer, TNBC is more likely to spread to the brain. When this occurs, it can cause neurological symptoms, which can vary depending on the location of the lesion. Symptoms can include:

  • Difficulty understanding or remembering things
  • Headaches
  • Seizures
  • Problems speaking
  • Odd behavior
  • Feelings of weakness or numbess
  • Loss of balance
  • Blurred vision

Metastasis to the brain is more likely in TNBC than in other types of breast cancer.

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Treating brain metastases in TNBC can be challenging, and they can significantly reduce a person’s chance of survival. In the Taiwanese study, researchers found that when TNBC spread to the brain first, the median survival was 4.3 months (ranging from 0.6 to 8 months). This was the lowest overall survival rate among all locations of metastasis.

Treatment Options for Metastatic TNBC

If you find out your TNBC has spread, your oncologist can help you better understand your treatment options. Their recommendations may differ depending on factors such as your medical history and the genetic mutations in your cancer cells.

If you’re just starting your initial cancer treatment, your health care provider may recommend chemotherapy as a first step. Although breast cancer cells can be killed by chemotherapy, TNBC doesn’t always respond to treatment, or it can grow back.

If you’ve already tried chemotherapy or if your cancer cells have specific proteins, your doctor may try another type of treatment. Immunotherapy drugs target specific proteins on the surface of cancer cells and harness your own immune system or synthetic immune proteins called monoclonal antibodies to attack them. For instance, sacituzumab govitecan-hziy (Trodelvy) contains a monoclonal antibody that targets and binds to a protein called trophoblast cell-surface antigen 2 (TROP2) on cancer cells. It then delivers a drug into the cell that causes its death. The drug is indicated to treat advanced or metastatic TNBC if surgery isn’t an option and after at least two other therapies have been tried.

Additionally, if you test positive for mutations in the BRCA1 or BRCA2 genes, a class of drugs called PARP inhibitors may be an effective cancer treatment. PARP inhibitors — which include drugs like olaparib (Lynparza) — can keep cancer cells from repairing themselves after being damaged by chemotherapy.

Even with available therapies, TNBC is still hard to treat. Breast cancer research is ongoing, and clinical trials will continue to find better ways to improve survival.

Read more about treatment options (and their potential side effects) for TNBC.

While you’re living with metastatic TNBC, it’s important to keep in touch with your cancer care team and let them know about any symptoms or side effects you’re experiencing. There are ways to manage these and feel better. Your quality of life is important.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 67,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Do you have metastatic triple-negative breast cancer? What symptoms of metastasis should others watch out for? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

References
  1. Metastatic and Triple-Negative Breast Cancer: Challenges and Treatment Options — Drug Delivery and Translational Research
  2. Overview of Recent Advances in Metastatic Triple Negative Breast Cancer — World Journal of Clinical Oncology
  3. Triple-Negative Breast Cancer — American Cancer Society
  4. Distant Metastasis in Triple-Negative Breast Cancer — Neoplasma
  5. Liver Metastatic Breast Cancer: Epidemiology, Dietary Interventions, and Related Metabolism — Nutrients
  6. Clinicopathological Features and Prognostic Evaluation of Bone Metastasis in Triple-Negative Breast Cancer — Journal of Cancer Research and Therapeutics
  7. Bone Metastasis — Mayo Clinic
  8. Predicting the Incidence and Prognosis of Bone Metastatic Breast Cancer: A SEER-Based Observational Study — BioMed Research International
  9. Survival Analysis and Prognosis of Patients With Breast Cancer With Pleural Metastasis — Frontiers in Oncology
  10. Symptoms of Secondary Breast Cancer — Cancer Research UK
  11. Incidence, Pattern and Prognosis of Brain Metastases in Patients With Metastatic Triple Negative Breast Cancer — BMC Cancer
  12. Treatment of Triple-Negative Breast Cancer — American Cancer Society
  13. Sacituzumab Govitecan Earns Full Approval for Triple-Negative Breast Cancer — National Cancer Institute
  14. Trodelvy Highlights of Prescribing Information — Gilead
  15. Triple Negative Breast Cancer: An Overview — Hereditary Genetics
  16. Brain Metastases Originating in Breast Cancer: Clinical-Pathological Analysis and Immunohistochemical Profile — Romanian Journal of Morphology and Embryology
    Posted on January 18, 2024
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    Maybell Nieves, M.D. graduated from Central University of Venezuela, where she completed medical school and general surgery training. Learn more about her here
    Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here

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